Targeting the LEDGF/p75 associated pathologies

Lukáš Vrzal1, Kateřina Čermáková1, Vanda Lux1, Subhalakshmi Sharma2, Jan De Rijck2, Milan Fábry3, Sara El Ashkar2, Frauke Christ2, Pavlína Řezáčová1, Zeger Debyser2, Václav Veverka1

1IOCB CAS, Flemingovo nam. 2, 166 10 Prague, Czech Republic, veverka@uochb.cas.cz
2KU Leuven, Molecular Virology and Gene Therapy, Leuven, Flanders, Belgium

3IMG CAS, Prague, Czech Republic

 

Lens Epithelium Derived Growth Factor/p75 (LEDGF/p75, or PSIP1) is a transcriptional co-activator that tethers other proteins to gene bodies. The chromatin tethering function of LEDGF/p75 is hijacked by HIV integrase to ensure viral integration at sites of active transcription. LEDGF/p75 is also important for the development of Mixed Lineage Leukemia (MLL), where it tethers the MLL1 fusion-complex at aberrant MLL targets to induce malignant transformation. In addition, LEDGF/p75 might be implicated in the Rett and MECP2 duplication syndromes (neurodevelopmental disorders). Here, we present the structural validation of the LEDGF/p75 binding interactions and targeting strategies for the LEDGF/p75 linked pathologies.